As a rule, commercially available natural lecithins are mixtures of various glycerophospholipids, for example phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl inositol, phosphatidyl serine and phosphatidic acid, of vegetable, animal or microbial origin, in which the proportions of the individual glycerophospholipids and of polar minor constituents can vary over a wide range. There are various methods available with which the proportions of certain glycerophospholipids in the natural mixtures can be increased, or with which the glycerophospholipids can be isolated in pure form.
Vegetable lecithins are usually by-products of the industrial production of vegetable oils from, for example, soybean, sunflower or rape seed. During the traditional refining process, so-called "degumming", the lecithins are obtained, together with vegetable oils (triglycerides), as so-called "raw lecithin", with an oil content between 50 and 70%. After a filtration step and standardisation to a certain lecithin content ("acetone insoluble"), these oil-containing raw lecithins can be used as emulsifiers, eg, in the production of food and of cosmetic and technical products.
For certain applications, however, oil-free lecithins are required, which dissolve better in water than do their oil-containing counterparts. The HLB value (as a measure of the solubility of an emulsifier in water, scale 1 [=insoluble in water] to 20 [=soluble in water]) of commercially available oil-free lecithins is about 7. However, the limited wettability of the deoiled lecithins in cold water poses a technical constraint.
Various methods have been described with which oil-free lecithins can be produced, also on an industrial scale. These include, in particular, solvent extraction with acetone or ethanol, and the more recent method of gas extraction with nearly-critical propane. From the point of view of potential solvent residues and the formation of by-products, extraction with compressed propane ranks as particularly advantageous, since, on the one hand, the processing conditions are mild on the product, and, on the other hand, propane is completely inert under the customary processing conditions. An added advantage consists in that the possible formation of undesired by-products can be entirely precluded. The disadvantage of this method, however, is that the water-wettability of lecithins deoiled with compressed propane is markedly inferior to that of corresponding acetone-deoiled qualities, and this puts distinct limitations on the practical applications.
The physiological importance of glycerophospholipids, and especially of phosphatidyl choline, as a component of biological membranes has been known for a long time. In the wake of numerous scientific studies in which lecithin was proved to have various beneficial effects in the human body, lecithins have been developed over the past few years which are intended especially as dietary supplements or as so-called nutraceuticals for a health-conscious consumer segment. In many cases lecithin fractions are used which have been enriched with certain glycerophospholipids, eg, fractions containing an elevated phosphatidyl choline content, which can be prepared, eg, by means of solvent extraction with ethanol. These products are usually offered in the form of powders, granules or tablets. In the production of lecithin-containing beverages, however, the limited solubility or dispersibility of the glycerophospholipids in water often constitutes a limitation, which is why, from a technical point of view, the production of oil-free lecithins with improved solubility or dispersibility in water is desirable. In the pharmaceuticals industry, due to traditionally good experience, use is made predominantly of lecithins obtained from eggs, and sometimes also of soya-based lecithins enriched with phosphatidyl choline. Besides peroral dosage forms, these lecithins are available in forms for intravenous administration, eg, as parenteral fat emulsions. On account of the high natural phosphatidyl choline content, fat-free egg-based lecithins are particularly suitable for drug formulations in reverse micelles (so-called liposomes). The range of applications of lecithins used pharmaceutically could also be enlarged if their solubility or dispersibility in water were improved.
Various methods are known for improving the solubility or dispersibility of lecithin in water. As was already mentioned, the water-solubility of natural lecithins is generally improved if they are freed as completely as possible of their oil content. In addition, chemical or enzymatic modifications have been suggested, eg, acetylation of the free amino groups by treating the lecithin with acetic anhydride, hydroxylation of the C.dbd.C double bonds of the unsaturated fatty acid radicals contained in lecithin, eg, with peracetic acid or hydrogen peroxide, acetylation of the amino groups with subsequent hydroxylation of C.dbd.C double bonds, and chemical or enzymatic partial hydrolysis, during which a fatty acid is split off from the phospholipid, to form so-called lyso-lecithins. Whereas--not least on account of legal stipulations--the first three of these modification processes have only been implemented in technical applications, the partially hydrolysed lyso-lecithins, by virtue of their being physiologically safe and of their resulting legislative acceptance, have enjoyed wide distribution during the past few years in food and in pharmaceutical active-ingredient formulations.
A decisive improvement in the water-dispersibility of lyso-lecithins can be achieved if they are likewise freed as completely as possible of their oil content. However, the production of these deoiled lyso-lecithins is extremely tedious, since besides the partial hydrolysis, there is the additional deoiling step, resulting in high costs for the overall process and consequently also for the product.
Native lecithins also differ in their physiological efficacy from chemically or enzymatically modified lecithins. In cases where lecithins are used pharmaceutically or as dietary supplements also on account of their natural physiological properties, products produced by way of modification processes are usually not suitable.
To improve the water-dispersibility of lecithins, a great variety of lecithin formulations have been proposed, eg, with ethanol/water (JP 81,163,745), with ethanol/propylene glycol/glycerol (JP 81,163,746), with ethanol/water/propylene glycol/glycerol (JP 81,163,747) and with sugar esters/propylene glycol (JP 75,30,595). What all of these formulations have in common is that relatively large amounts of additives are required in order to obtain a suitable pasty consistency for the further incorporation of the emulsifier formulations. This has the disadvantage that the surface-active lecithin, the actual emulsifying active ingredient in the formulation, is heavily diluted, and relatively large amounts of surface-active formulation aids are introduced into the mixture.
In view of these disadvantages of the prior art, the object of this invention was thus to provide oil-free glycerophospholipid formulations which show enhanced solubility and/or dispersibility in water, as well as a suitable method of producing them, while avoiding the shortcomings and limitations of already-known products and their production methods.
This object was established with oil-free formulations which contain a homogeneous mixture of (a) one or more glycerophospholipids and (b) one or more anhydrous, liquid polyol compounds with at least two hydroxyl groups, the components (a) and (b) being present in a molar ratio of 1:0.1 to 1. The average molecular weights of the glycerophospholipids can be used as the calculation basis for this molar ratio.
Surprisingly, it was found that the solubility and dispersibility of oil-free lecithins in water can be improved significantly by mixing them homogeneously with polyol compounds in the proportions cited. The formulations of the invention are, for one, extremely stable in water and do not dissociate into their individual components, and, for the other, they dissolve distinctly better in water than do the corresponding oil-free lecithins currently on the market.